Scot E. Moss

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: VI. Retinal Photocoagulation

The prevalence of focal and panretinal photocoagulation and its relationship to demographic and other characteristics were examined in a population-based study in southern Wisconsin. For participants whose age at diagnosis was less than 30 years and who were taking insulin (996 persons) the prevalence rate of panretinal photocoagulation (13.9%) was higher than that of focal photocoagulation (3.6%). For those whose age at diagnosis was 30 years or older (1370 persons), the prevalence rate for panretinal photocoagulation (3.6%) was slightly higher than that of focal photocoagulation (3.0%). Seventy-two percent of eyes of younger onset and 45% of eyes of older onset persons that had received panretinal photocoagulation treatment were found to have incomplete regression of retinal new vessels, and in approximately half of these eyes severe proliferative retinopathy (Diabetic Retinopathy Study High Risk Characteristics [DRS-HRC]) was present. Among eyes with DRS-HRC, 55% were found to be untreated.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: IV. Diabetic Macular Edema

The prevalence of macular edema and its relationship to a number of risk factors were examined in a population-based study in southern Wisconsin. Macular edema was determined from its presence on stereoscopic fundus photographs or from past history as recorded and documented in clinic records and photographs. For participants whose age at diagnosis of diabetes was less than 30 years and who were taking insulin (n = 919), prevalence rates of macular edema varied from 0% in those who had diabetes less than 5 years to 29% in those whose duration of diabetes was 20 or more years. In these persons, macular edema was associated with longer duration of diabetes, presence of proteinuria, diuretic use, male gender and higher glycosylated hemoglobin. For those whose age at diagnosis was 30 years or older (n = 1121), prevalence rates of macular edema varied from 3% in those who had diabetes less than 5 years to 28% in those whose duration of diabetes was 20 or more years. In these persons, presence of macular edema was associated with longer duration of diabetes, higher systolic blood pressure, insulin use, higher glycosylated hemoglobin, and presence of proteinuria.

The Wisconsin epidemiologic study of diabetic retinopathy: XVII: The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes1

OBJECTIVE To examine the 14-year incidence and progression of diabetic retinopathy and macular edema and its relation to various risk factors. DESIGN Population-based incidence study. SETTING The study was conducted in an 11-county area in southern Wisconsin. PARTICIPANTS Six hundred thirty-four insulin-taking persons with diabetes diagnosed before age 30 years participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. MAIN OUTCOME MEASURES The 14-year progression of retinopathy, progression to proliferative retinopathy, and incidence of macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. RESULTS The 14-year rate of progression of retinopathy was 86%, regression of retinopathy was 17%, progression to proliferative retinopathy was 37%, and incidence of macular edema was 26%. Progression of retinopathy was more likely with less severe retinopathy, being male, having higher glycosylated hemoglobin or diastolic blood pressure at baseline, an increase in the glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of proliferative retinopathy or incidence of macular edema was associated with more severe baseline retinopathy, higher glycosylated hemoglobin at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examination. The increased risk of proliferative retinopathy was associated with the presence of hypertension at baseline, whereas the increased risk of a participant having macular edema develop was associated with the presence of gross proteinuria at baseline. Lower glycosylated hemoglobin at baseline was associated with improvement in retinopathy. CONCLUSIONS These data suggest relatively high 14-year rates of progression of retinopathy and incidence of macular edema. These data also suggest that a reduction of hyperglycemia and hypertension may result in a beneficial decrease in the progression to proliferative retinopathy.

Ten-year Incidence of Visual Loss in a Diabetic Population

PURPOSE The purposes of this study are to estimate the 10-year incidence of blindness and visual loss in a diabetic population, examine risk factors for visual loss, and examine temporal trends in rates of blindness and visual loss. METHODS The design is a population-based cohort study, which includes 891 younger-onset persons with diabetes, 485 persons with older-onset diabetes who are taking insulin, and 502 persons with older-onset diabetes who are not taking insulin and who participated in baseline, 4-year, and 10-year examinations. The main outcome measures are incidence of blindness (visual acuity, 20/200 or worse), doubling of the visual angle, and visual impairment (visual acuity, 20/40 or worse). RESULTS The 10-year incidences of blindness were 1.8%, 4.0%, and 4.8% in persons in the younger-onset, older-onset taking insulin, and older-onset not taking insulin groups, respectively. Respective 10-year rates of visual impairment were 9.4%, 37.2%, and 23.9%. Rates for doubling of the visual angle were similar. Doubling of the visual angle was more common in women with older-onset diabetes and in persons with younger-onset and older-onset diabetes who were taking insulin and who had higher glycosylated hemoglobin or proteinuria levels. The presence of macular edema or more severe retinopathy was associated with more visual loss in all three groups. Smoking was associated with visual loss in persons with younger-onset diabetes, and systolic blood pressure was associated in persons with older-onset diabetes who were taking insulin. Rates of blindness and doubling of the visual angle decreased in persons with younger-onset diabetes in the second part of the follow-up. In the older-onset groups, only the rate of blindness declined. These decreases could not be explained entirely by treatment or mortality. CONCLUSIONS Several modifiable risk factors are associated with loss of vision. Although visual loss is still common in this diabetic population, the incidence of blindness may be decreasing.

Visual impairment in diabetes.

Visual acuity was measured in a population-based study of diabetic retinopathy in southern Wisconsin. Persons diagnosed prior to 30 years of age and taking insulin (younger onset, n = 996) and those diagnosed at 30 years of age or older (older onset, n = 1370) were examined. Best corrected visual acuity was determined using the Early Treatment of Diabetic Retinopathy Study protocol. In the younger onset group, 1.4% had moderate visual impairment (best corrected visual acuity in the better eye of 20/80 to 20/160) and 3.6% were legally blind (visual acuity in the better eye of 20/200 or worse). Visual impairment in this group was associated with older age at examination, longer duration of diabetes, presence of proliferative retinopathy, and presence of senile cataracts. In the older onset group, 3.0% had moderate visual impairment and 1.6% were legally blind. Visual impairment in this group was associated with older age at examination, longer duration of diabetes, presence of senile cataract, presence of macular edema, and proliferative diabetic retinopathy. When assigning causes of impaired vision, diabetic retinopathy was responsible in part for 86% of eyes with visual acuity of 20/200 or worse in younger onset persons and for 33% in older onset persons.

An Alternative Method of Grading Diabetic Retinopathy

The purpose of this report is to present a system for grading the severity of diabetic retinopathy that is a rapid, relatively inexpensive, and standardized alternative to the more detailed Early Treatment Diabetic Retinopathy Study (ETDRS) system; present data on its reproducibility; and compare it to the detailed ETDRS grading system. The alternative system was used to grade fundus photographs obtained during a large prevalence study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The alternative method involved grading seven stereoscopic standard fields as a whole, and assigning a level of severity for the eye according to the greatest degree of retinopathy using a modified Airlie House Classification scheme. Using an eight-level classification system of increasing severity of retinopathy, there was 78.3% exact agreement between the alternative and ETDRS systems. A grader regraded all 503 disagreements, and was in exact agreement 49.3% of the time with the alternative system, 35.7% of the time with the detailed system, and 15.0% with neither the alternative or detailed systems. Interobserver agreement for the alternative system was 78.5%; intraobserver agreement over a 9 month to 1 year period was 90.0% for grader 1 and 84.0% for grader 2. The alternative system of grading, when used by experienced graders, is a reproducible method for objectively determining retinopathy status in epidemiologic studies.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XIII. Relationship of Serum Cholesterol to Retinopathy and Hard Exudate

Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 for the Wisconsin Epidemiologic Study of Diabetic Retinopathy. There was a significant trend for increasing severity of diabetic retinopathy and of retinal hard exudate with increasing cholesterol in insulin-using persons. Cholesterol levels were not related to the severity of either ocular condition in older-onset patients. High-density lipoprotein-cholesterol was unrelated to the severity of either lesion. In multiple logistic regression analyses, cholesterol was not a significant factor in describing the severity of retinopathy in any group but was a significant factor in describing the severity of retinal hard exudate. Glycosylated hemoglobin and diastolic blood pressure were significant descriptors of the severity of retinopathy in younger-onset patients in these multivariate analyses. Diastolic blood pressure added significantly to explaining the severity of hard exudate in older-onset insulin users. These data support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids.

Epidemiology of Proliferative Diabetic Retinopathy

OBJECTIVE This review examines recent epidemiological data about the prevalence and incidence of and risk factors for proliferative diabetic retinopathy. In addition, the relation of proliferative retinopathy to other systemic complications associated with diabetes is reviewed. RESEARCH DESIGN AND METHODS The data come mostly from the baseline and 4-yr follow-up examinations of a large population-based study, the WESDR, which involved 996 younger-onset insulin-dependent people whose diabetes was diagnosed at < 30 yr of age and 1370 older-onset people whose diabetes was diagnosed at ≥ 30 yr of age, and who were taking or not taking insulin. RESULTS The major finding is that proliferative retinopathy is a prevalent complication (23% in the WESDR younger-onset group, 10% in the WESDR older-onset group that takes insulin, and 3% in the group that does not take insulin). Hyperglycemia, longer duration of diabetes, and more severe retinopathy at baseline were associated with an increased 4-yr risk of developing proliferative retinopathy. However, higher blood pressure at baseline was associated only with the development of proliferative retinopathy in the younger-onset group. The presence of proliferative diabetic retinopathy was associated with an increased 4-yr risk of loss of vision, cardiovascular disease, diabetic nephropathy, and mortality. In the WESDR, a significant number of diabetic people with proliferative retinopathy at risk for vision loss were not under the care of an ophthalmologist or had not undergone panretinal photocoagulation. CONCLUSIONS These data suggest that hyperglycemia and, possibly, high blood pressure are related to proliferative retinopathy. They also suggest that once proliferative diabetic retinopathy is detected, people should have a medical evaluation, because it is a strong indicator for the presence and development of systemic disease. These data also indicate that diabetic patients and their physicians should be aware of the need for routine ophthalmological examinations to detect and treat proliferative retinopathy.

Relation of Glycemic Control to Diabetic Microvascular Complications in Diabetes Mellitus

Little information is available comparing the incidence and progression of chronic diabetic complications among persons with insulin-dependent diabetes mellitus (IDDM) and those with noninsulin-dependent diabetes mellitus (NIDDM) [1-4]. Such comparisons have been limited by the difficulty in accurately classifying the type of diabetes and by the paucity of studies in which persons with IDDM or NIDDM were assessed concurrently using the same standardized objective methods (such as masked grading of stereoscopic fundus photographs). Epidemiologic data show that the natural history of retinopathy is similar in both types of diabetes [2, 5-8]; however, the prevalence is higher and the severity is greater in persons with IDDM than in those with NIDDM [5, 6]. When loss of vision is present, it is more likely to be associated with proliferative retinopathy in those with IDDM and with macular edema in those with NIDDM [9, 10]. In both types of diabetes, early detection and treatment of proliferative retinopathy and clinically significant macular edema is estimated to prevent 95% of occurrences of substantial loss of vision [11]. However, data from epidemiologic studies suggest that vision-threatening retinopathy is often not detected in a timely fashion in persons with either type of diabetes [12-14]. The pathologic changes characterizing diabetic nephropathyglomerular basement membrane thickening and expansion of the glomerular mesangiumare similar in IDDM and NIDDM [3]. Data from some studies suggest that the risk for developing diabetic nephropathy is higher in IDDM, but other studies have found the risk to be similar in IDDM and NIDDM [15-22]. Although renal dialysis and transplantation have been shown to prolong life and improve its quality in both types of persons, the treatment is costly and not without serious short- and long-term complications. Less is known about the epidemiology of diabetic neuropathy in persons with IDDM and NIDDM. Data from one study suggest similar prevalences of symptomatic polyneuropathies in both types of diabetic persons, although those with IDDM had a higher frequency of a more severe stage of polyneuropathy than those with NIDDM [23]. However, a cross-sectional multicenter study of English diabetic patients showed that the prevalence of neuropathy in persons with NIDDM was higher (32%) than in those with IDDM (23%) [24]. The Diabetes Control and Complications Trial (DCCT) has shown that intensive management and control of hyperglycemia is of benefit in preventing the incidence and progression of diabetic retinopathy; loss of vision; the need for photocoagulation treatment; and the incidence of microalbuminuria, gross proteinuria, and diabetic neuropathy in persons with IDDM [25]. To date, no definitive clinical trial data have shown that glycemic control is of similar benefit in preventing these complications in persons with NIDDM. The purpose of this article is to examine the relation of hyperglycemia to the long-term incidence and progression of diabetic retinopathy, gross proteinuria, end-stage renal disease, and history of neuropathy in persons with either IDDM or NIDDM using data from a large, population-based study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Such information may help in determining whether information derived from persons with IDDM in the DCCT can be used to make recommendations about intensive glycemic control in persons with NIDDM. Methods WESDR Population The WESDR population has been described in detail in other publications [2, 5-8]. In brief, the population included a probability sample selected from 10 135 diabetic patients who received primary care in an 11-county area in southern Wisconsin from 1979 to 1980. This sample included a younger-onset group (all patients were diagnosed before 30 years of age and were taking insulin, and almost all had IDDM [n = 1210]) and an older-onset group (a sample of persons [n = 1780]) stratified by duration of diabetes, of whom 824 were taking insulin (a mixture of persons with either IDDM or NIDDM) and 956 were not (all had NIDDM). Among the younger-onset group, 996 participated in the baseline examination (1980 to 1982), 891 in the 4-year follow-up, and 765 in the 10-year follow-up. Of the 1780 eligible older-onset persons, 1370 participated in the baseline examination, 987 in the 4-year follow-up, and 533 in the 10-year follow-up. The population was 98.6% white. The reasons for nonparticipation and comparisons among participants and nonparticipants at baseline and the 4-year and 10-year follow-up examinations have been presented elsewhere [2, 5-8]. The main reason for nonparticipation in both groups over the 10-year course of the study was death. Procedures The baseline and follow-up examinations were done in a mobile examination van in or near the city where the participants lived. The ocular and physical examinations included measuring visual acuity using a modification of the Early Treatment Diabetic Retinopathy Study protocol [26], measuring blood pressure using the Hypertension Detection and Follow-up Program protocol [27], testing of urine for gross proteinuria (0.3 g/L or more) using a dipstick (Labstix, Ames, Iowa), administering a structured interview by examiners, taking stereoscopic color fundus photographs of the Diabetic Retinopathy Study seven standard fields [28], and measuring hemoglobin A1 ([HbA1] A1a, A1b, and A1c) using a microcolumn technique [29]. The normal range for glycated hemoglobin was 4.6% to 7.9%. Its coefficient of variation was 2.4%. The WESDR HbA1 microcolumn results compare with the DCCT HbA1c results as follows: DCCT = 0.003 + 0.935 (WESDR). Grading protocols have been described in detail elsewhere and are modifications of the Early Treatment Diabetic Retinopathy Study adaptation of the modified Airlie House Classification scheme of diabetic retinopathy [12]. Definitions The severity scale for diabetic retinopathy is defined as follows. Level 10 represents no retinopathy, levels 21-53 represent nonproliferative retinopathy of increasing severity, and levels 60-80 represent proliferative retinopathy of increasing severity. The retinopathy level of a patient was derived by giving the eye with the higher level greater weight. Patients in a given level were divided into two groups: those with the same level in each eye and those with a lesser level in one eye. For example, the level for a participant with level 21 retinopathy in each eye was specified by the notation level 21/21. This scheme provides a 15-step scale (10/10, 21/< 21, 21/21, 31/< 31, 31/31, 37/< 37, 37/37, 43/< 43, 43/43, 47/< 47, 47/47, 53/< 53, 53/53, 60+/< 60+, and 60+/60+). The incidence of any retinopathy was estimated from all persons who had no retinopathy at the baseline examination (severity level 10/10) and who participated in the follow-up examination(s) (n = 261 for younger-onset persons, 146 for older-onset persons taking insulin, and 301 for older-onset persons not taking insulin). Progression to proliferative retinopathy was estimated from all persons who were free of this complication at the baseline examination (n = 712 for younger-onset persons, 417 for older-onset persons taking insulin, and 487 for older-onset persons not taking insulin). For persons with nonproliferative or no retinopathy, progression was defined as an increase in the severity of retinopathy by two steps or more at either of the follow-up examinations (n = 712 for younger-onset persons, 417 for older-onset persons taking insulin, and 487 for older-onset persons not taking insulin). Presence of macular edema was defined as thickening of the retina with or without partial loss of transparency within one disc diameter from the center of the macula. The incidence was estimated from all persons who had no macular edema and had not been previously treated with photocoagulation at baseline (n = 688 for younger-onset persons, 329 for older-onset persons taking insulin, and 444 for older-onset persons not taking insulin). For each eye, the best-corrected visual acuity was recorded as the number of letters read correctly from 0 ( 20/250) to 70 (20/10). Loss of vision was defined as a doubling of the visual angle (a loss of 15 letters or more, for example, a change from 55 to 40 letters, which corresponds to a visual acuity change from 20/20 to 20/40). The incidence of proteinuria was estimated from all persons who had less than 0.30 g/L urine protein concentration at the baseline examination and who participated in the follow-up examination(s) (n = 666 for younger-onset persons, 376 for older-onset persons taking insulin, and 418 for older-onset persons not taking insulin). Incidence of proteinuria was defined as a urine protein concentration of 0.30 g/L or more at either of the follow-up examinations. The incidence of renal failure was defined as being on renal dialysis or having had a renal transplantation at one of the follow-up examinations in all persons with a urine protein concentration less than 0.30 g/L at the baseline examination (n = 666 for younger-onset persons, 376 for older-onset persons taking insulin, and 418 for older-onset persons not taking insulin). The incidence of loss of tactile sensation or loss of temperature sensitivity was defined as reporting a history of these complications at one of the follow-up examinations in persons who did not have them at the baseline examination (n = 444 for younger-onset persons, 148 for older-onset persons taking insulin, and 258 for older-onset persons not taking insulin). Data Analysis To determine the relative risks and 95% confidence intervals for the incidence and progression of retinopathy, the baseline glycated hemoglobin level was divided into quartiles for each group. Tests for trends in rates were done by the Mantel-Haenszel procedure stratified on time period [30]. Multivariate analyses for predicting incidence of any retinopathy, progression of retin

Effect of Pregnancy on Progression of Diabetic Retinopathy

A prospective study was undertaken to determine the effect of pregnancy on diabetic retinopathy. Insulin-taking diabetic women were enrolled; one group was comprised of pregnant women, the other group was comprised of women who were not pregnant. Women were evaluated on referral and again in the postpartum period. The severity of diabetic retinopathy was based on grading of fundus photographs of seven standard photographic fields. The glycosylated hemoglobin, duration of diabetes, current age, diastolic blood pressure, number of past pregnancies, and current pregnancy status were evaluated as risk factors for progression of diabetic retinopathy. After adjusting for glycosylated hemoglobin, current pregnancy was significantly associated with progression (P < 0.005, adjusted odds ratio 2.3). Diastolic blood pressure had a lesser effect on the probability of progression. The findings from this study indicate that pregnancy and level of glycemia are associated with progression of diabetic retinopathy.